JOURNAL OF CHEMICAL RESEARCH 2012 245
Entry
R
3
R
4
Isolated yield/%
5a
5b
6a
6b
7a
7b
8a
8b
OAc
H
OAc
H
OAc
H
OH
H
H
OAc
H
OAc
H
OAc
H
OH
65
67
94
90
91
89
77
68
Scheme 1 Strategy for the rapid synthesis of a 2-deoxy-2-acetonyl sugar from its natural sugar.
Reagents and conditions: a, Ac O, pyridine, rt, 24 h; b, Ac O, 33% HBr, AcOH/acetic acid, rt, 12 h; c, Zn, saturated NaH
rt, 12 h; d, NIS, toluene/acetic acid, 80 °C, 10 min; e, methallyltributyltin, AIBN, benzene, 80 °C, 4 h; f, OsO -NaIO
dioxane-H O, rt, 4 h; g, MeONa, MeOH, rt, 6 h, pH 9.0.
2
2
2
PO
4
4
/acetone,
4
, 2,6-lutidine
2
J = 4.0, 4.0 Hz), 4.09 (dd, 1H, J = 8.0, 4.0 Hz), 4.21 (dd, 1H, J = 4.0,
Synthesis of compound 7; general procedure
2
5
.4 Hz), 4.29 (dd, 1H, J = 4.0, 4.4 Hz), 4.45 (dd, 1H, J = 8.0, 8.0 Hz),
.37 (dd, 1H, J = 12.0, 8.0 Hz), 5.49 (d, 1H, J = 12.0 Hz); C NMR
2,6-Lutidine (119.9 µL, 1.036 mmol), OsO4 (2.5% in 2-methyl-2-
13
propanol, 130.7 µL, 0.011 mmol), and NaIO (222.0 mg, 1.037 mmol)
4
(
7
CDCl ), δ 170.20, 169.54, 169.59, 168.17, 91.99, 74.78, 72.04,
were added sequentially to a solution of compound 6a (200.0 mg,
0.518 mmol) in 20 mL of dioxane-water (3:1). The reaction mixture
was stirred at room temperature for 4 h. Then the mixture was concen-
trated under pressed pressure, and the residue was partitioned between
3
C
0.48, 61.21, 28.77, 22.85, 20.99, 20.75, 20.60. HRESIMS: Calcd for
+
C H IO Na [M+Na] m/z 481.2013; found m/z 481.2009.
14
19
9
Synthesis of compound 6; general procedure
CHCl (200 mL) and water (200 mL). The organic layer was washed
3
Compound 5a (500.0 mg, 1.091 mmol) was dissolved in (10 mL)
anhydrous benzene and the reaction mixture was degassed by bub-
bling Ar through the solution for 30 min. Then methallyltributyltin
with ice water and saturated NaHCO solution, and then dried over
3
Na SO and concentrated under reduced pressure. The residue was
2
4
purified by chromatography (hexanes/EtOAc, 3:1) to afford com-
(
3.7 g, 10.916 mmol) and AIBN (50.0 mg, 0.304 mmol) were added
1
pound 7a (184 mg, 91%) as a light yellow solid. H NMR (CD OD),
3
under Ar. The reaction mixture was heated at 81 °C for 4 h. Then the
reaction mixture was cooled to room temperature, concentrated under
reduced pressure, and the residue was partitioned between CH CN
δH 1.93 (s, 3H), 1.95 (s, 3H), 1.99 (s, 3H), 2.02 (s, 3H), 2.06 (s, 3H),
2
.37 (m, 3H), 3.32 (s, 1H), 3.93 (dd, 1H, J = 6.8, 2.0 Hz), 4.13
3
(dd, 1H, J = 8.0, 4.4 Hz), 4.79 (dd, 1H, J = 9.6, 9.6 Hz), 5.15 (dd, 1H,
(
200 mL) and pentane (200 mL). The CH CN layer was washed with
J = 10.0, 9.6 Hz), 5.74 (d, 1H, J = 6.4 Hz); 13C NMR (CD OD), δC
3
3
pentane (100 mL×2), concentrated under reduced pressure and puri-
fied by chromatography (hexanes/EtOAc 5:1) to afford compound 6a
(
1
3
4
5
206.37, 170.43, 170.24, 169.82, 169.08, 93.58, 73.05, 71.87, 69.31,
62.14, 41.42, 40.79, 29.95, 28.06, 26.88, 20.84, 20.84. HRESIMS:
1
+
396 mg, 94%) as a clear syrup. H NMR (CD OD), δ 1.69 (s, 3H),
Calcd for C
3
H
H O Na [M+Na] m/z 411.3662; found m/z 411.3658.
17
24 10
.92 (s, 3H), 1.94 (s, 3H), 1.99 (s, 3H), 2.03 (s, 3H), 2.06 (m, 3H),
.32 (s, 1H), 3.92 (dd, 1H, J = 2.0, 2.0 Hz), 4.14 (dd, 1H, J = 6.4,
.4 Hz), 4.54 (s, 1H), 4.63 (s, 1H), 4.78 (dd, 1H, J = 9.6, 9.6 Hz),
Compound 7b (178 mg, 89%) was prepared similarly to afford a light
1
yellow syrup.
H NMR (DMSO-D6), δ 1.89 (s, 3H), 1.97 (s, 3H),
H
1
2
.99 (s, 3H), 2.01 (s, 3H), 2.06 (s, 3H), 2.10 (m, 3H), 2.13 (s, 1H),
.38 (d, 1H, J = 4.0 Hz), 2.49 (dd, 1H, J = 3.2, 5.2 Hz), 3.95 (m, 2H),
13
.13 (dd, 1H, J = 10.0, 9.6 Hz), 5.69 (d, 1H, J = 8.8 Hz); C NMR
(
CD OD), δ 170.78, 170.45, 170.19, 169.41, 143.69, 112.28, 94.52,
3 C
4.13 (dd, 1H, J = 6.4, 6.4 Hz), 4.99 (dd, 1H, J = 3.2, 3.2 Hz), 5.13 (dd,
7
2
3.98, 71.82, 69.73, 62.51, 42.68, 37.30, 22.14, 21.34, 21.29, 21.18,
1H, J = 2.8, 6.4 Hz), 5.74 (d, 1H, J = 2.8 Hz); 13C NMR (DMSO-D6),
+
1.18. HRESIMS: Calcd for C H O Na [M+Na] m/z 409.3942;
δC 206.37, 170.08, 169.97, 169.57, 168.77, 93.65, 70.92, 70.72, 65.58,
18
26
9
found m/z 409.3944. Compound 6b (356 mg, 90%) was prepared and
isolated as light yellow syrup. H NMR (CDCl ), δ 1.79 (s, 3H), 1.98
61.57, 54.92, 36.22, 29.83, 20.51, 20.50 20.45, 20.39. HRESIMS:
1
+
3
H
Calcd for C H O Na [M+Na] m/z 411.3662; found m/z 411.3659.
17
24 10
(s, 3H), 2.00 (s, 3H), 2.03 (s, 3H), 2.04 (s, 3H), 2.15 (m, 3H), 4.03
(d, 1H, J = 12.0 Hz), 4.05 (s, 1H), 4.22 (dd, 1H, J = 4.0, 2.0 Hz), 4.72
(d, 2H, J = 8.0 Hz), 4.96 (dd, 1H, J = 4.0, 8.0 Hz), 4.99 (d, 1H,
Synthesis of compound 8; general procedure
Sodium methoxide (5 mg) was added to a solution of compound 7a
(184 mg, 0.474 mmol) in of methanol (20 mL). The reaction mixture
was stirred at room temperature for 6 h. Then the mixture was concen-
trated under pressed pressure. The residue was purified by chromato-
graphy (CH Cl /MeOH, 13:1) to afford compound 8a (80.3 mg, 77%)
13
J = 4.0 Hz), 5.78 (dd, 1H, J = 4.6, 4.0 Hz); C NMR (CD OD), δ
1
6
HRESIMS: Calcd for C H O Na [M+Na] m/z 409.3942; found m/z
4
3
C
70.28, 169.55, 169.51, 169.19, 142.11, 114.56, 97.60, 72.82, 71.98,
8.82, 62.73, 41.21, 36.91, 21.91, 21.15, 21.05, 20.76, 20.05.
+
18
26
9
2
2
1
09.3938.
as a colourless syrup. H NMR (D O), δ 2.12 (m, 1H), 2.14 (s, 3H),
2 H